Synthesis And Biological Activity Of Protohematoxylin A Derivatives

Protosappanin A,which is an effective component of sappan L as a traditional medicine plant,has antitumor,immunosuppressive effects and anti-HIV-1 integrase activities.Synthesis of protosappanin A and its'derivatives have not been reported in the literatures.The biological activities of protosappanin A and its derivatives could not be systematically studied.It is very important to synthesize derivatives of protosappanin to meet the research of biological activities.Firstly,a synthetic route of derivatives of protosappanin A was designed.The derivatives of protosappanin A was prepared by iodination,condensing etherification,intramolecular C-H activation/C-C cyclization,carbonyl addition,reduction and Tiffeneau-Demjanov rearrangement.The best approaches of key reaction step in the synthetic route were optimized,including iodination,condensing etherification,intramolecular C-H activation/C-C cyclization and carbonyl addition.25 derivatives of protosappanin A were synthesized by the synthesis scheme.Structures of all products and intermediates were confirmed by ¹H NMR and ¹³C NMR.Antitumor activity and structure-activity relationship of derivatives of protosappanin A were researched and evaluated.The results showed that 3-fluoro-protosappanin A and 3,11-difluoro-protosappanin A have good antitumor effect on human hepatoma Heg P2 cells,in which 3,11-difluoro-protosappanin A was superior to3-fluoro-protosappanin A.